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Foci of Programmed Cell Death-Ligand 1 (PD-L1)-positive Tumor Areas With Tumor-infiltrating Leukocytes (TILs) Evocative of a PD-1/PD-L1-related Adaptive Immune Resistance are Frequent in Merkel Cell Carcinoma

Foci of Programmed Cell Death-Ligand 1 (PD-L1)-positive Tumor Areas With Tumor-infiltrating... Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis have revolutionized the treatment of patients with Merkel cell carcinoma (MCC). To date, no biomarker conditions access to these ICIs in MCC. We compared the tumor microenvironment of PD-L1+ and PD-L1− areas in a case series of MCC searching for foci evocative of PD-1/PD-L1 adaptive immune resistance. Among 58 tumors studied on digitalized serial tissue sections, 11 (19%) were concluded as “PD-L1+ tumors” [≥1% positive tumor cells (TCs) using PD-L1 immunohistochemistry in the whole tumor slide]. In addition, among the remaining 47 (81%) “PD-L1− tumors,” we nevertheless also identified “PD-L1+ FOV” (ie, “field of view” of about 3 mm² containing ≥1% positive TCs) in 22 (38%) additional tumors. Comparison between paired “PD-L1+ field of view (FOV)” and “PD-L1− FOV” within tumors, and between “PD-L1+ tumors” and “PD-L1− tumors”, revealed correlations between PD-L1 positivity and the abundance of tumor-infiltrating leukocytes, arguing for areas of PD-1/PD-L1-related adaptive immune resistance at least in some foci of “PD-L1+ tumors” and also in “PD-L1− tumors.” Tumor heterogeneity consists in a challenge searching for biomarkers able to predict the response/nonresponse to ICIs. Progress in digital pathology and multiplex immunolabeling may permit to overcome this challenge by better analyzing the interactions between TCs and immune and nonimmune non-TCs in the same tissue section. This approach of tumor heterogeneity may contribute to elucidate and to predict why some patients respond impressively to ICIs, whereas others do not. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Immunohistochemistry & Molecular Morphology Wolters Kluwer Health

Foci of Programmed Cell Death-Ligand 1 (PD-L1)-positive Tumor Areas With Tumor-infiltrating Leukocytes (TILs) Evocative of a PD-1/PD-L1-related Adaptive Immune Resistance are Frequent in Merkel Cell Carcinoma

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References (24)

Publisher
Wolters Kluwer Health
Copyright
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
1541-2016
DOI
10.1097/PAI.0000000000000792
Publisher site
See Article on Publisher Site

Abstract

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis have revolutionized the treatment of patients with Merkel cell carcinoma (MCC). To date, no biomarker conditions access to these ICIs in MCC. We compared the tumor microenvironment of PD-L1+ and PD-L1− areas in a case series of MCC searching for foci evocative of PD-1/PD-L1 adaptive immune resistance. Among 58 tumors studied on digitalized serial tissue sections, 11 (19%) were concluded as “PD-L1+ tumors” [≥1% positive tumor cells (TCs) using PD-L1 immunohistochemistry in the whole tumor slide]. In addition, among the remaining 47 (81%) “PD-L1− tumors,” we nevertheless also identified “PD-L1+ FOV” (ie, “field of view” of about 3 mm² containing ≥1% positive TCs) in 22 (38%) additional tumors. Comparison between paired “PD-L1+ field of view (FOV)” and “PD-L1− FOV” within tumors, and between “PD-L1+ tumors” and “PD-L1− tumors”, revealed correlations between PD-L1 positivity and the abundance of tumor-infiltrating leukocytes, arguing for areas of PD-1/PD-L1-related adaptive immune resistance at least in some foci of “PD-L1+ tumors” and also in “PD-L1− tumors.” Tumor heterogeneity consists in a challenge searching for biomarkers able to predict the response/nonresponse to ICIs. Progress in digital pathology and multiplex immunolabeling may permit to overcome this challenge by better analyzing the interactions between TCs and immune and nonimmune non-TCs in the same tissue section. This approach of tumor heterogeneity may contribute to elucidate and to predict why some patients respond impressively to ICIs, whereas others do not.

Journal

Applied Immunohistochemistry & Molecular Morphology – Wolters Kluwer Health

Published: Jan 1, 2020

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